选择性和非选择性 COX-2 抑制剂在小鼠体内的药效学和药代动力学比较

Taimaa Yahya, Yaareb Mousa
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引用次数: 0

摘要

如今,兽医领域需要副作用小、疗效好的非甾体抗炎药。本研究旨在比较小鼠体内选择性(尼美舒利)和非选择性(阿司匹林)COX-2 抑制剂的药效学(镇痛和对 COX-2 的抑制)和药代动力学。采用上下法评估中位有效剂量、尼美舒利和阿司匹林的 COX-2 活性和血浆浓度及其在小鼠体内的药代动力学特征。通过热板法发现,尼美舒利和阿司匹林的中位有效剂量(ED50s)分别为 7.9 毫克/千克和 212.23 毫克/千克。尼美舒利(15.8 毫克/千克,静注)和阿司匹林(424.5 毫克/千克,静注)都能通过降低小鼠血浆、肝脏和肾脏中 COX-2 的浓度来抑制 COX-2 的活性,与对照组(阴性和阳性)和阿司匹林处理组相比,尼美舒利的抑制作用更强。尼美舒利(15.8 毫克/千克,静注)在 0.5、1、2、4 和 24 小时不同可比时间段的血浆浓度分别为 14.62、9.22、9.88、7.38 和 2.27 微克/毫升,高于阿司匹林,而阿司匹林(424.5 毫克/千克,静注)在相同测量时间段的血浆浓度分别为 4.35、3.17、2.54、2.25 和 1.21 微克/毫升。尼美舒利的药代动力学变量估计为:AUC0-∞ 169.18、AUMC0-∞ 2358、72、Kel 0.06、Cmax 14.62、Tmax 0.5、t1/2β 11.07、MRT 13.94、Vss 1.49、Cl 0.09,而阿司匹林药代动力学参数差异分别为 82.31、2428.32、0.03、4.35、0.5、21.25、158.12、5.16。研究认为,尼美舒利具有比阿司匹林更优越的药理特性(镇痛、解热和抗炎),这是因为尼美舒利能够更有选择性地抑制 COX-2,并且在小鼠体内具有独特的药代动力学,这可能会在兽医学中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacodynamic and Pharmacokinetic Comparison between Selective and Non-selective COX-2 Inhibitors in Mice
Nowadays, there is a need for good and efficacious NSAIDs with minimal side effects to be applied in veterinary medicine. The aim was to compare the pharmacodynamics (analgesia and inhibition of COX-2) and pharmacokinetics between selective (nimesulide) and non-selective (aspirin) COX-2 inhibitors in mice. Assessing the median effective doses by using the up-and-down method, COX-2 activity and plasma concentrations for both nimesulide and aspirin with their pharmacokinetic profiles in mice. The median effective doses (ED50s) of nimesulide and aspirin were found to be 7.9 and 212.23 mg/kg, respectively, using the hot-plate. Both nimesulide (15.8 mg/kg, i.m.) and aspirin (424.5 mg/kg, i.m.) inhibited COX-2 activity through a decrease in COX-2 concentrations in the plasma, liver, and kidney of mice, with superior inhibition when administering nimesulide in comparison to the control (negative and positive) and aspirin-treated groups. Plasma concentrations of nimesulide (15.8 mg/kg, i.m.) measured for different comparable periods of 0.5, 1, 2, 4, and 24 hours were higher than those of aspirin, which were 14.62, 9.22, 9.88, 7.38 and 2.27 µg/ml, respectively, while aspirin (424.5 mg/kg, i.m.) was 4.35, 3.17, 2.54, 2.25 and 1.21 µg/ml, at the same measured times. Nimesulide pharmacokinetic variables were estimated to be AUC0-∞ 169.18, AUMC0-∞ 2358,72, Kel 0.06, Cmax 14.62, Tmax 0.5, t1/2β 11.07, MRT 13.94, Vss 1.49, and Cl 0.09, while aspirin pharmacokinetic parameters differed to be 82.31, 2428.32, 0.03, 4.35, 0.5, 21.25, 158.12, and 5.16, respectively. The study concluded that nimesulide has superior pharmacological properties (analgesic, antipyretic, and anti-inflammatory) than aspirin due to its ability to inhibit COX-2 more selectively and its unique pharmacokinetics in mice, which may be useful in veterinary medicine.
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